Regulation of DAPK1 by Natural Products: An Important Target in Treatment of Stroke

Noori, Tayebeh; Shirooie, Samira; Sureda, Antoni; Sobarzo‐Sánchez, Eduardo; Dehpour, Ahmad Reza; Saldías, Marianela; Akkol, Esra Küpeli

doi:10.1007/s11064-022-03628-7

Cited by 5 publications

(3 citation statements)

References 158 publications

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“…The death-associated protein kinase (DAPK) family is one of the important families of serine/threonine kinases involved in regulating certain biological functions in human cells. Past studies have demonstrated the inhibition of TNF-α and IL-1β expression via modulation of DAPK1 signaling in stroke ( Noori et al, 2022 ). Therefore, TNF-α and IL-18 were selected in this experiment to explore the spectrum-effect relationship of YYTNG in MCAO rats.…”

Section: Discussionmentioning

confidence: 99%

Spectrum effect correlation of yangyin tongnao granules on cerebral ischemia-reperfusion injury rats

Zhang

Yang

et al. 2022

Front. Pharmacol.

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Yangyin Tongnao Granules (YYTNG), as traditional Chinese medicine (TCM) compound preparation, have a good curative effect on cerebral ischemia-reperfusion injury. This study aimed to investigate the relationship between the active components of YYTNG in the plasma and the inflammatory response in cerebral ischemia-reperfusion injury rats. High-performance liquid chromatography (HPLC) was conducted to determine the fingerprints at different time points of middle cerebral artery occlusion (MCAO) rats after the administration of YYTNG at different times points. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) in the plasma of MCAO rats at different time points. The spectral-effect relationship between the YYTNG fingerprints and inflammatory indexes in vivo was established by combining three different mathematical models, grey correlation, multiple linear regression, and partial least-square method. The results revealed that each chromatographic peak in the HPLC of the plasma exhibited a certain correlation with the inflammatory index, in the following order: P2 >P6 >P5 >P1 >P3 >P4. Therefore, this study successfully established the spectrum-effect correlation of YYTNG on cerebral ischemia-reperfusion injury rats. The results provide a certain guiding ideology for the analyses of the relationship between fingerprints and the pharmacodynamics of TCM prescriptions.

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Section: Discussionmentioning

confidence: 99%

Spectrum effect correlation of yangyin tongnao granules on cerebral ischemia-reperfusion injury rats

Zhang

Yang

et al. 2022

Front. Pharmacol.

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“…Natural compounds represent an important resource for the discovery of therapeutic chemicals for various neurological diseases. Flavonoids are widely distributed bioactive molecules in nature and possess diverse biological effects such as anti-oxidative stress and anti-inflammation by interacting with key signaling molecules in the cell [ 213 ]. Yokoyama et al first measured the binding affinity of 17 natural flavonoids to DAPK1 using the 1-anilinonaphthalene-8-sulfonic acid (ANS) competitive assay.…”

Section: Dapk1 As a Target For Disease-modifying Treatment Of Admentioning

confidence: 99%

Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease

Zhang,

Kim,

Lee

2024

Transl Neurodegener

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Alzheimer’s disease (AD) is the most prevalent form of dementia in the elderly and represents a major clinical challenge in the ageing society. Neuropathological hallmarks of AD include neurofibrillary tangles composed of hyperphosphorylated tau, senile plaques derived from the deposition of amyloid-β (Aβ) peptides, brain atrophy induced by neuronal loss, and synaptic dysfunctions. Death-associated protein kinase 1 (DAPK1) is ubiquitously expressed in the central nervous system. Dysregulation of DAPK1 has been shown to contribute to various neurological diseases including AD, ischemic stroke and Parkinson’s disease (PD). We have established an upstream effect of DAPK1 on Aβ and tau pathologies and neuronal apoptosis through kinase-mediated protein phosphorylation, supporting a causal role of DAPK1 in the pathophysiology of AD. In this review, we summarize current knowledge about how DAPK1 is involved in various AD pathological changes including tau hyperphosphorylation, Aβ deposition, neuronal cell death and synaptic degeneration. The underlying molecular mechanisms of DAPK1 dysregulation in AD are discussed. We also review the recent progress regarding the development of novel DAPK1 modulators and their potential applications in AD intervention. These findings substantiate DAPK1 as a novel therapeutic target for the development of multifunctional disease-modifying treatments for AD and other neurological disorders.

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“…A large number of studies have proven that DAPK1 plays an Important role in mediating the pathological process of acute and chronic neurological disorders, such as Alzheimer’s disease (AD) [ 9 , 17 , 18 , 19 , 20 ], Parkinson’s disease (PD) [ 21 , 22 ], Huntington’s disease (HD) [ 23 ], traumatic brain injury (TBI) [ 24 , 25 ], stroke [ 15 , 26 , 27 , 28 ], and epilepsy [ 10 , 11 ]. We discovered that levels of DAPK1 are significantly increased in the hippocampi of 75% of AD patients compared to those in control subject samples [ 17 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Ablation of Death-Associated Protein Kinase 1 Changes the Transcriptomic Profile and Alters Neural-Related Pathways in the Brain

Zhi

Lan

et al. 2023

IJMS

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Death-associated protein kinase 1 (DAPK1), a Ca2+/calmodulin-dependent serine/threonine kinase, mediates various neuronal functions, including cell death. Abnormal upregulation of DAPK1 is observed in human patients with neurological diseases, such as Alzheimer’s disease (AD) and epilepsy. Ablation of DAPK1 expression and suppression of DAPK1 activity attenuates neuropathology and behavior impairments. However, whether DAPK1 regulates gene expression in the brain, and whether its gene profile is implicated in neuronal disorders, remains elusive. To reveal the function and pathogenic role of DAPK1 in neurological diseases in the brain, differential transcriptional profiling was performed in the brains of DAPK1 knockout (DAPK1-KO) mice compared with those of wild-type (WT) mice by RNA sequencing. We showed significantly altered genes in the cerebral cortex, hippocampus, brain stem, and cerebellum of both male and female DAPK1-KO mice compared to those in WT mice, respectively. The genes are implicated in multiple neural-related pathways, including: AD, Parkinson’s disease (PD), Huntington’s disease (HD), neurodegeneration, glutamatergic synapse, and GABAergic synapse pathways. Moreover, our findings imply that the potassium voltage-gated channel subfamily A member 1 (Kcna1) may be involved in the modulation of DAPK1 in epilepsy. Our study provides insight into the pathological role of DAPK1 in the regulatory networks in the brain and new therapeutic strategies for the treatment of neurological diseases.

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Regulation of DAPK1 by Natural Products: An Important Target in Treatment of Stroke

Cited by 5 publications

References 158 publications

Spectrum effect correlation of yangyin tongnao granules on cerebral ischemia-reperfusion injury rats

Spectrum effect correlation of yangyin tongnao granules on cerebral ischemia-reperfusion injury rats

Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease

Ablation of Death-Associated Protein Kinase 1 Changes the Transcriptomic Profile and Alters Neural-Related Pathways in the Brain

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